The Effects of Guanfacine on Context Processing Abnormalities in Schizotypal Personality Disorder

Background: The signature of impaired cognition in people with schizotypal personality disorder (SPD) may be centrally related to working memory impairments. Guanfacine, an α_2A agonist that acts post-synaptically in the prefrontal cortex (PFC), has shown potential for reducing working memory limitations in other populations. This study examined the potential of guanfacine for improving context processing, a feature of working memory, in SPD. Methods: 29 individuals with SPD entered into a 4-week, randomized parallel-design, double-blind, placebo-controlled trial of guanfacine treatment, followed by a 4-week open-label extension. A modified version of the AX-Continuous Performance Test (AX-CPT) was administered. On this task, evidence of intact context processing includes few BX errors (false cue, correct probe) and higher levels of AY errors (correct cue, false probe). Results: At the end of double-blind treatment, participants treated with guanfacine demonstrated a significant reduction in BX errors and a small but significant increase in AY errors, a pattern that was not seen in the participants treated with placebo. Conclusions: SPD participants improved in their context processing toward a normal response bias, making fewer BX and more AY errors, after being treated with guanfacine.